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Analysis of the mechanisms related to differences in the progression of motor deficits between Wistar and SHR (spontaneously hypertensive rat) rats submitted to pharmacological models of Parkinson's Disease

Grant number: 15/12308-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2016
Effective date (End): May 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Regina Helena da Silva
Grantee:Anderson Henrique França Figueredo Leão
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The Parkinson Disease (PD) is characterized as a motor disease related to aging. Nevertheless not being the most frequent neurodegenerative disease, behind only Alzheimer's disease, it currently afflicts 1-2% of the world population above 60 years old. Thus, countries with increasing life expectancy, as Brazil, consider PD an important public health burden. The epidemiology of PD involves intrinsic and extrinsic risk factors, which define the chances to develop the illness. Punctual mutations and polymorphisms with functional significance are considered as predisposing genetic factors, while exposition to pesticides and toxins are highlighted as environmental factors. Nevertheless, few studies with animal models focus on the interaction between these factors. This could be reached submitting different rat lineages to a same chemical insult to the dopaminergic transmission. For example, rats from different strains that express different behavioral and neurochemical profile to the dopaminergic transmission - as Wistar and SHR (Spontaneusly Hypertensive Rat) - can provide new insights to cellular mechanisms of resistance to PD. In this sense, recently we characterized the motor deficit progression induced by a repeated reserpine treatment in Wistar and SHR, and found that SHR rats are resilient to the progression of motor deficits, and that there are differences in expression of tyrosine hydroxylase and ±-synuclein between strains. In view of these findings, we are aiming to investigate and extend the molecular, neurochemical and genetic steps associated to the differences to the motor deficit progression between these strains. Additionally, we will investigate the differences between strains to the induction of the parkinsonian phenotype by another dopamine-depleting agent, the 6-OHDA. The confirmation of such differences to PD induction susceptibility, as its mechanisms, will help to identify novel cellular targets to treatment and/or neuroprotection against PD progression. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MACEDO, PRISCILA TAVARES; AQUINO, ANTONIO C. Q.; MEURER, YWLLIANE S. R.; BRANDAO, LUIZ E. M.; CAMPELO, CLARISSA L. C.; LIMA, RAMON H.; COSTA, MARCOS R.; RIBEIRO, ALESSANDRA M.; SILVA, REGINA H.. Subtle Alterations in Spatial Memory Induced by Amyloid Peptides Infusion in Rats. FRONTIERS IN AGING NEUROSCIENCE, v. 10, . (15/12308-5)
LEAO, ANDERSON H. F. F.; MEURER, YWLLIANE S. R.; DA SILVA, ANATILDES F.; MEDEIROS, ANDRE M.; CAMPELO, CLARISSA L. C.; ABILIO, VANESSA C.; ENGELBERTH, ROVENA C. G. K.; CAVALCANTE, JEFERSON S.; IZIDIO, GEISON S.; RIBEIRO, ALESSANDRA M.; et al. Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and alpha-Synuclein Expression. FRONTIERS IN AGING NEUROSCIENCE, v. 9, . (15/12308-5, 15/03354-3)
DAS CHAGAS CAMPELO, CLARISSA LOUREIRO; SILVA, REGINA HELENA. Genetic Variants in SNCA and the Risk of Sporadic Parkinson's Disease and Clinical Outcomes: A Review. PARKINSONS DISEASE, . (15/12308-5)
CAMPELO, CLARISSA L. C.; CAGNI, FERNANDA C.; FIGUEREDO, DIEGO DE SIQUEIRA; OLIVEIRA, JR., LUIZ G.; SILVA-NETO, ANTONIO B.; MACEDO, PRISCILA T.; SANTOS, JOSE R.; IZIDIO, GEISON S.; RIBEIRO, ALESSANDRA M.; DE ANDRADE, TIAGO G.; et al. Variants in SNCA Gene Are Associated with Parkinson's Disease Risk and Cognitive Symptoms in a Brazilian Sample. FRONTIERS IN AGING NEUROSCIENCE, v. 9, . (15/12308-5)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.